1. Field of the Invention
The present invention relates to an evaluation system, an evaluation method, and an evaluation program for evaluating HER2 protein development by analyzing and processing HER2 protein immunohistochemical staining pathological image data.
2. Description of the Related Art
HER2 (Human Epidermal Growth Factor Receptor Type 2) is an oncogene which exists in the 17-th chromosome length arm.
Cancer is more susceptible to metastasis and return when amplification of HER2 gene is recognized, or excessive development of HER2 protein coded by HER2 gene is recognized. In this event, it is said that the prognosis is bad. Accordingly, the determination of HER2 is very important.
It has been reported that the excessive development of HER2 gene or HER2 protein occurs in breast cancer of human patients. It has been further known that the excessive development of HER2 gene or HER2 protein occurs in bladder cancer and ovarian cancer except for breast cancer.
HER2 testing methods include the immunohistochemistry staining method (IHC method) which determines whether or not excessive development of HER2 protein has occurred, and a method of evaluating the amplification of HER2 gene (FISH method: fluorescence in situ hybridization).
The IHC method is currently most widely used in HER testing. The IHC method is an approach which detects a target protein which localizes within cells and tissues by utilizing a peculiar coupling reaction of an antigen-antibody reaction. A coloring matrix, which is called DAB (diaminobenzidine) for dyeing HER2 protein into brown, is used to dye immunity substance.
In many IHC methods, HER2 protein is caused to develop color by DAB, and the nucleus is dyed into blue by hematoxylin.
HER2 protein localizes in cell membranes of cancer cells. Therefore, when the HER2 test is conducted, cell membranes are dyed in positive cells.
Then, the score is evaluated at four levels of “0,” “1+,” “2+,” and “3+” according to its chromaticity.
Scores “0” and “1+” are called negative, while scores “2+” and “3+” are called positive. A portion that is subjected to determination of Her2 status is an invasion portion. The chromaticity of breast-intraductal extension and cytoplasm is not evaluated.
The diagnosis on the HER2 test is performed according to the following procedure.
First, an HE dye (hematoxylin eosin dye) sample of a tissue slice is observed using a microscope to perform a tumor diagnosis.
Also, a tissue slice adjacent to an HE dyed tissue slice is dyed by immunohistochemistry using an antibody of HER2 to derive a tissue slice sample.
This tissue slice sample is matched with a portion within the HE dyed sample which has been determined as a tumor portion. This matching identifies a tumor portion within the tissue slice sample which has been dyed according to immunohistochemistry.
Subsequently, the tumor portion is observed using a microscope.
This pathological test is one of the approaches generally conducted in current medical institutions.
In recent years, automatic dyeing machines are pervasive for dyeing a tissue slice. Thus, the number of pathological tests has been increased. On the other hand, the number of pathologists who conduct the pathological tests is overwhelmingly smaller.
In the HER2 test, a pathologist visually determines and evaluates the development of dyed positive cells through microscope observation. Accordingly, the determination result, i.e., results based on the evaluation of the HER2 test cannot be reproduced, the test lacks objectivity, and is semi-quantitative.
Also, even in the event of employing a system for displaying image information of a slide on a display, the evaluation and determination are visually performed by a pathologist. Accordingly, the results based on the evaluation of the HER2 test cannot be reproduced, the test lacks objectivity, and is semi-quantitative.
Non-Patent Document 1 (Yutaka Hatanaka, Kaoru Hashizume et al., Quantitative immunohistochemical evaluation of HER2/neu expression with HercepTest™ in breast carcinoma by image analysis, Pathology International, 2001, vol. 51, pp. 33-36) describes a measurement method which involves reading a microscopic image, quantifying HER2 protein deposits, the immunity tissue of which has been chemically dyed, and making an image analysis.
In this method, the quantification is performed using the ratio of an area dyed in brown to an area dyed in blue.
The pathologist visually evaluates and determines the development of dyed positive cells in a microscopic observation. Accordingly, the results of the HER2 test, determined by the pathologist, cannot be reproduced, the test lacks objectivity and are semi-quantitative.
In the method described in Non-Patent Document 1, quantification is performed using the ratio of an area dyed in brown to an area dyed in blue.
However, the HER2 determination involves determining the chromaticity of cell membranes. Therefore, even if a region dyed in blue by hematoxylin is evaluated, HER2 determination cannot be properly accomplished. Also, the evaluation is also made on portions dyed in brown, except for cell membranes in which HER2 protein develops, disadvantageously leading to erroneous evaluations.